Glutamate receptors (pink spots) concentrate at sites of synaptic contact on a hippocampal neuron dendrite. Changes in the abundance of these receptors alter synaptic transmission in the aged brain.

Michael Ehlers, Duke University

Our work should provide important information on why older individuals are so vulnerable to neurodegenerative diseases. And we’ll try to define the therapeutic targets that are most important for older patient populations.

Aging of the Nervous System

Although it wasn’t realized for generations, it’s now clear that the living body is always working on the wiring. That has long been established fact, of course, for the peripheral nervous system, which runs our fingers, toes, tongue and arms. For the sake of survival in the face of peril, quick and effective repairs are needed in the extremities, where injury is common. So the peripheral nervous system has evolved great ability to maintain continuity, ready to grow new cells and redo the wiring to circumvent any damage that results from injury.

But the central nervous system, meaning the brain and spinal cord, is different, and medical wisdom held that no new brain cells, neurons, are made after early childhood. In other words, what you got was all you’ll get.

Now that’s clearly not true. Modern research has demonstrated that the brain also contains stem cells, a supply of immature cells that can be called on to grow, differentiate and become new neurons. This shows that the brain does have some “plasticity,” that the capacity exists to repair some kinds of damage.

But it’s also clear that major brain repairs don’t happen often. There seems to be no natural repair that restores the spinal cord after injury. Nor is major loss of certain brain cells repaired, such as the losses that lead to Alzheimer’s disease and Parkinson’s disease. Even when neural stem cells are present, somehow they fail to make adequate repairs.

So that’s where the clarity ends, at least for now. Much has yet to be learned.

Fortunately, the tools that are being focused on neurobiology are improving dramatically. Active MRI allows researchers to observe the brain while it’s thinking, or responding to various stimuli. New approaches to microscopy, precision laser ablation of individual cells and capillaries, and genetic engineering of model organisms are opening new vistas for exploring the brain and how it works.

So right now, ever more powerful and precise research methods are being applied to animals such as soil worms, fruit flies and mice, in which researchers can study nerve connections, neurotransmitter chemicals, genetic alterations, and stem cell responses. Where the brain was once a black box we were trying to influence with magic, a few viewing ports have been created where scientists are taking a peek.

Still, a major barrier that’s been hard to penetrate is the brain’s tremendous complexity. It’s hard to find a window that reveals much about the billions of neurons, plus glial cells and others, that make up the brain. Also, each of these billions of neurons makes multiple connections to others at the complex junctures called synapses. And within the brain the synapse maps are constantly being revised and rearranged as the cells make new connections and break others. How this occurs, why it occurs and what can go wrong are all questions that are being asked, but are difficult to answer. Hidden within all the complexity, of course, is the learning process, several different types of memory, and the roots of neurodegenerative diseases that often occur with aging.

But there is reason for optimism. The pace of research is accelerating. The new tools of biotechnology are extraordinarily precise and powerful. And the people doing the work are asking good questions, getting interesting answers, and making steady progress.